Background: Medication nonadherence is the highest determinant of relapse and rehospitalization in schizophrenia. Therefore, interventions that empower patients to remain on medication for extended periods would substantially improve clinical outcomes using existing medications. The investigators previously developed a proof of concept long-term implantable delivery system using the typical antipsychotic agent haloperidol. Need: However, feedback from patients, families and physicians indicates that a long-term delivery system using a newer atypical antipsychotic medication would be preferable. Research Project: In response to previous reviews, the current proposal is now limited to 2 years to demonstrate an in vitro/in vivo correlation model for sterilized biodegradable Risperidone implants before proceeding to more costly toxicological, behavioral and molecular characterization studies. Studies were designed in consultation with the FDA Psychopharmacology team and would be performed in collaboration with the NIMH drug synthesis program. The first Aim will demonstrate in vitro release characteristics for a prototype antipsychotic medication from sterile implants made from 8 polymers at a single drug load. The second Aim will determine in vivo Risperidone serum concentration from each of these single-polymer implants. Dr. Louise Dube has joined our team to bring expertise in Clinical Psychopharmacology for ADME modeling. Environment: Studies will be conducted at the Center for Experimental Therapeutics in Psychiatry at the University of Pennsylvania under the direction of Steven J. Siegel MD, PhD. This program has a longstanding collaboration with Dr. Karen I. Winey in the Department of Material Science at The University of Pennsylvania. Investigators now have the required expertise and background in clinical psychiatry, Psychopharmacology and polymer engineering to accomplish the proposed research program. Industry R&D and pharmacokinetic modeling consultants have been included to further augment the research team. Future studies would evaluate the toxicological effects of a long-term subcutaneous delivery system as well as assessing molecular, neurochemical and behavioral measures to thoroughly evaluate long-term effects of Risperidone implants. Completion of the proposed studies would foster future industrial investment in long-term delivery systems for multiple agents, leading to dramatically improved patient care in the future. [unreadable] [unreadable] [unreadable]